Novel SEQaBOO Study of Newborn Hearing Loss Foretells Role for Obstetricians in Genomic Medicine

The ear of a newborn baby only a few weeks old.As genetic and genomic sequencing become incorporated into newborn screening for hearing loss, patients may look to obstetricians for guidance on genetic testing decisions.

Auditory screening of newborns, mandated by most states in recent decades, now reaches an estimated 98 percent of newborns in the United States and has significantly reduced the average age for identifying congenital deafness. But adding genetic testing could drive more accurate diagnosis and personalized management during infancy’s critical window when the brain’s speech and language center is developing rapidly.

To this end, medical geneticist Cynthia Morton, PhD, director of cytogenetics at Brigham and Women’s Hospital, has launched SEQaBOO (SEQuencing a Baby for an Optimal Outcome). This first-of-its kind study is offering genome sequencing for trios (Mom, Dad and newborn) when the newborn does not pass newborn hearing screening. The goals of SEQaBOO include learning how genomics will be received by parents and its potential as a new frontier in personalized medicine for hearing loss. Knowing the cause of a child’s deafness can help to direct the most appropriate interventions, such as hearing aids, cochlear implants or sign language instruction.

“We need the most information about the underlying etiology right from the start,” said Morton. “We hope that implementing genomic sequencing into newborn screening for hearing loss will reduce the time frame for determining how to best manage care.”

Morton and colleagues aim to enroll approximately 100 otherwise healthy babies annually who are born at Brigham and Women’s Hospital. In addition, newborns referred to Boston Children’s Hospital and Massachusetts Eye and Ear for their confirmation audiometry will be enrolled. Approximately 3 in 1,000 newborns are born with permanent hearing loss, and by school age approximately 1 in 100 children have mild or unilateral hearing loss. Hearing loss can be caused by genetic factors, infection or injury.

Morton, whose research lab has had a longstanding interest in the genetic causes of hearing loss, is the Kenneth J. Ryan, MD, distinguished chair in the hospital’s Department of Obstetrics and Gynecology.

More than 150 genes are known to contribute to hearing loss, and as many as 800 could ultimately play a role in hearing. Identifying variants early in life could help clinicians refine care and avoid unnecessary testing, Morton explained, using two examples: For a newborn who has a common genetic variation that is tied to deafness at birth, but is not known to cause structural abnormalities, an otolaryngologist may opt not to order a diagnostic CT scan. Or, if a baby is known to have a genetic variant that is associated with hearing loss in the presence of certain antibiotics, that information may be crucial for preserving hearing.

A Role for Obstetricians in Guiding Parent Decision-Making on Genetic Testing?

The SEQaBOO research study will provide insight into how patients may look to their obstetricians to address the implications of genetic screening. The study’s multiple aims include:

  • investigating the feasibility of incorporating genomic sequencing (GS) into newborn screening with hearing loss as a model;
  • comparing diagnostic yields and clinical management of the genetic screening cohort to the standard-of-care; and
  • seeking to understand parental attitudes toward GS.

Of 75 families enrolled in SEQaBOO to date, about half are enrolled for both genomic sequencing (of both parents and their child) and surveys; the others are participating in the surveys only. “We’re trying to learn: What makes one couple more or less interested in participating than others?” Morton said.

Morton noted that compared to other newborn GS efforts, parents seem to be more eager to consent when a phenotype — such as hearing loss — is under evaluation.

Lessons from 1.2 Million Genetic Screenings in China

In research outside the United States, Morton and colleague Jun Shen, PhD, of Brigham and Women’s Department of Pathology, have been involved in a recently-published study in Genetics in Medicine of a cohort of 1.2 million newborns in China who were screened for 20 hearing-loss-related genetic variants. The researchers concluded that “Incorporating genetic screening improves the effectiveness of newborn hearing screening programs by elucidating etiologies, discerning high-risk subgroups for vigilant management, identifying additional children who may benefit from early intervention, and informing at-risk newborns and their maternal relatives of increased susceptibility to ototoxicity.”

As efforts continue to incorporate genetic testing into newborn screening for hearing loss, Morton said she is optimistic about broad public acceptance: “Everyone understands what it means to hear versus not hear. I think most people can understand the value of using genetic testing for identifying hearing loss as soon as possible to facilitate optimal habilitation.”